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Results for “Prefrontal Cortex”

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At least 595 records · Page 33Linked to original sources

PubMed2005

Brain activation gradients in ventrolateral prefrontal cortex related to persistence of ADHD in adolescent boys.

OBJECTIVE: To explore the possible role that functional abnormalities of the prefrontal cortex and basal ganglia play in the persistence of attention-deficit/hyperactivity disorder (ADHD) in adolescents aged 15 to 19 years. METHOD: Ten male adolescents who were diagnosed with ADHD during childhood were grouped into those who continued to meet full diagnostic criteria for DSM-IV ADHD (persisters; n = 5) and those in whom symptoms had remitted sufficiently to warrant a diagnosis of ADHD in partial remission (remitters; n = 5). Persisters, remitters, and five carefully matched controls with no history of ADHD were scanned using functional magnetic resonance imaging while performing a go/no-go task. RESULTS: Parallel linear trends were found in performance on the go/no-go task and activation of ventrolateral prefrontal cortex, such that persisters made the most commission errors (33%) and showed the greatest activation, remitters made fewer commission errors (24%) and had lower activity, and activation was lowest in controls who made the fewest errors (13%). CONCLUSIONS: These preliminary results suggest that developmental changes in ADHD symptomatology are associated with functional changes in ventrolateral prefrontal cortex activity.

Adolescent↗

PubMed2003

D1 dopamine receptors in the mouse prefrontal cortex: Immunocytochemical and cognitive neuropharmacological analyses.

Dopamine D1 receptors have critical neuromodulatory influences on the working memory functions of the prefrontal cortex, a brain region affected in many neuropsychiatric disorders. When D1 receptor agents are administered to rats or monkeys performing working memory tasks, an "inverted U" dose/response function is typically observed, whereby either too little or too much D1 receptor stimulation impairs working memory. There are two subtypes of D1 receptors, the D1A and the D1B (also known as the D1 and D5, respectively), but the relative contributions of these subtypes to prefrontal cortical function are not known, as there are no pharmacological agents that can distinguish between these receptors. Thus, genetically altered mice are needed to address this question. However, it is not known whether the mouse prefrontal cortex contains both D1A and D1B receptor subtypes, nor is it known whether mice will exhibit responses to D1 receptor agonists similar to those seen in rats and monkeys. The current study examined these issues by immunostaining the mouse brain with specific antibodies directed at the D1A and D1B receptor subtypes and by assessing the effects of increasing doses of a D1 receptor agonist, SKF81297, on spatial working memory performance in mice. Results indicate that mice are generally similar to monkeys and rats, expressing both D1A and D1B receptors in the prefrontal cortex and exhibiting an inverted "U" dose/response curve when administered SKF81297.

Animals↗

PubMed1978

Subcortical afferents to the prefrontal cortex in rabbits.

The origins of cells projecting to the prefrontal cortex of the rabbit were studied, using horseradish peroxidase (HRP) technique. HRP injected into the prefrontal cortex labeled cells in the basal forebrain, lateral hypothalamus, raphe nuclei and locus coeruleus area on both sides. Labeled cells appeared also in the nucleus medialis dorsalis of the thalamus and other thalamic nuclei on the injection side.

Afferent Pathways↗

PubMed1981

Prefrontal cortex of the mouse defined as cortical projection area of the thalamic mediodorsal nucleus.

In the mouse small amounts of horseradish peroxidase were injected iontophoretically into different portions of the frontal lobe. Out of a large number of mice, 18 with typical injections which together covered most of the anterior half of the cortex were selected, and their retrogradely labeled thalamic cells were described and illustrated in detail. Special emphasis was laid on the cortical projections of the mediodorsal nucleus which were considered to define locus and extent of the prefrontal cortex. The results reveal that topographically the extent of the mouse, prefrontal cortex closely resembles that of the rat, another species of the rodent order. It includes a small area within and dorsal to the rhinal sulcus and a comparatively larger region within the medial half of the anterior cortex. Furthermore, the dorsal tip of the frontal pole is reached by a considerable number of afferents from the mediodorsal nucleus. Whether this last projection also exists in the rat is still disputed. As in the rat, only the sulcal prefrontal cortex seems to be reached by mediodorsal cells alone, whereas the rest of the prefrontal cortical fields have overlapping projections from the anteromedial nucleus. Though a considerable area within the frontal lobe of the mouse is reached by mediodorsal afferents, the significance and usefulness of this definition of the prefrontal cortex is questioned.

Animals↗

PubMed1986

Neurotransmitters, pathways and circuits as the neural substrates of self-stimulation of the prefrontal cortex: facts and speculations.

Through a multidisciplinary approach considerable progress has been made in understanding the neural substrates of self-stimulation (SS) of the medial prefrontal cortex (MPC). Thus, neuroanatomical studies have revealed that intrinsic neurones in the MPC seem to be the central elements responsible for initiating and maintaining this phenomenon in this area of the brain. Complementary to this central finding are the electrophysiological and neurohistological data reviewed here, showing that neurones in the MPC are directly activated and have monosynaptic feed-back connections with neurones located in areas which also support SS. These findings have given rise to the hypothesis that several single feed-back pathways or single circuits exist between points of SS in the MPC and points of SS in other areas of the brain. This hypothesis implies that SS in a particular area would depend not only on the intrinsic local activity induced by the electrical stimulation but on the functional and specific activity of other nuclei in the brain. The fact that lesions of single circuits, which are apparently involved in SS of the MPC such as the medial prefrontal cortex-ventrotegmental area-medial prefrontal cortex and medial prefrontal cortex-n. dorsomedialis of the thalamus-medial prefrontal cortex, do not produce a permanent decrease of SS, together with the finding that transynaptic connections seem to exist between MPC and other areas of the brain, suggests further that a complex rather than several single independent circuits could be at the neural basis of SS of the MPC. If that were the case, then SS of the MPC would not only depend upon local and single feed-back activity but upon specific functional feed-back activity among the nuclei, which in turn have single feed-back connections with the MPC (see the concept of 'complex circuit' outlined in the section of Behavioural studies). On the basis of this hypothesis no permanent changes should be expected after lesions of single pathways since physiological and even anatomical compensation could be reached through the rest of the undamaged circuit. That terminals containing specific neurotransmitters exist in layers of the PC where electrodes for SS are located has been reviewed in this paper. Some of these neurotransmitters have been suggested to be part of the local substrates activated by SS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

Synaptic density of the prefrontal cortex regulated by dopamine instead of serotonin in rats.

Recent findings indicate that monoamine contributes to synaptic plasticity. We examined the synaptic density of the prefrontal cortex and parietal cortex of rats using dopamine (DA) antagonists and agonists, as well as serotonin (5-HT) depleters and found a reduction in synaptic density in the prefrontal cortex lamina V-VI at a maximum of 20% with administration of a D1 antagonist (SCH23390) and at a maximum of 30% with a D2 antagonist (YM09151). Further, with the administration of D1+D2 antagonists there was a 27% decrease in synaptic density, which was a larger reduction than the total of the single dosages of each DA antagonist at equal levels. Increase in synaptic density was seen at a maximum of 8.5% with dosage of a D1 agonist (SKF38390) and 14.5% with dosage of a D2 agonist (PPHT). The dosage of D1+D2 agonists showed a 27.1% increase in synaptic density. There was no change in synaptic density of the parietal cortex with either DA antagonist or agonist administration. Administration of 5-HT depleter pCPA resulted in a 13.8% reduction of synaptic density in the parietal cortex, though there was no change identified in the synaptic density in the prefrontal cortex. Based on these results, it was suggested that the area of the brain with affected synaptic plasticity could differ, depending on the type of monoamine.

Animals↗

PubMed2004

Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.

RATIONALE: Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior. OBJECTIVES: Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients. METHODS: We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded. RESULTS: Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. CONCLUSIONS: This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.

Adult↗

PubMed2003

Dopaminergic D2 receptor activation modulates FGF-2 gene expression in rat prefrontal cortex and hippocampus.

We have investigated the role of dopaminergic receptors in modulation of basic fibroblast growth factor (FGF-2) expression in rat prefrontal cortex and hippocampus, two brain regions important for cognition. We found that FGF-2 expression is upregulated by quinpirole, a D2 agonist, in prefrontal cortex and to a lesser extent in hippocampus. This modulation was specific for dopamine D2 receptors because no effect was observed when the dopamine D1 and D3 agonists, SKF38393 and 7-OH-DPAT, respectively, were administered. Our findings show that activation of dopaminergic D2 receptors modulates FGF-2 expression in rat prefrontal cortex and hippocampus. Our data highlight the complex modulation of FGF-2 expression in limbic areas pointing to this trophic molecule as a putative target of drugs used against acute and chronic neurodegenerative diseases such as Parkinson's disease.

Animals↗

PubMed1996

Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset.

Using a primate analogue of the Wisconsin Card Sort Test, this study demonstrated, for the first time, that lesions of the prefrontal cortex in monkeys produce a qualitatively similar impairment in attentional set-shifting to that seen following prefrontal cortical damage in humans. Although damage to the prefrontal cortex did not disrupt the ability of marmosets, a New World monkey, to maintain an attentional set, it did disrupt their ability to shift an attentional set. It also impaired their performance on discrimination reversal, object retrieval, and spatial delayed response, consistent with the effects of prefrontal damage in Old World monkeys. Comparison of the cognitive processes underlying discrimination reversal, object retrieval, and attentional set-shifting reveals the various types of inhibitory control provided by the prefrontal cortex.

Animals↗

PubMed1996

Pyramidal neurons in rat prefrontal cortex show a complex synaptic response to single electrical stimulation of the locus coeruleus region: evidence for antidromic activation and GABAergic inhibition using in vivo intracellular recording and electron microscopy.

Cognition and acquisition of novel motor skills and responses to emotional stimuli are thought to involve complex networking between pyramidal and local GABAergic neurons in the prefrontal cortex. There is increasing evidence for the involvement of cortical norepinephrine (NE) deriving from the nucleus locus coeruleus (LC) in these processes, with possible reciprocal influence via descending projections from the prefrontal cortex to the region of the LC. We used in vivo intracellular recording in rat prefrontal cortex to determine the synaptic responses of individual neurons to single electrical stimulation of the mesencephalic region including the nucleus LC. The most common response consisted of a late-IPSP alone or preceded by an EPSP. The presence of an early-IPSP following the EPSP was sometimes detected. Analysis of the voltage dependence revealed that the late-IPSP and early-IPSP were putative K(+)- and Cl- dependent, respectively. Synaptic events occurred following short delays and were inconsistent with the previously reported time for electrical activation of unmyelinated LC fibers. Moreover, systemic injection of the adrenergic antagonists propranolol (beta receptors), or prazosin (alpha 1 receptors), did not block synaptic responses to stimulation of the LC region. Finally, certain neurons were antidromically activated following electrical stimulation of this region of the dorsal pontine tegmentum. Taken together, these results suggest that the complex synaptic events in pyramidal neurons of the prefrontal cortex that are elicited by single electrical stimulation of the LC area are mainly due to antidromic activation of cortical efferents. Further insight into the chemical circuitry underlying these complex synaptic responses was provided by electron microscopic immunocytochemical analysis of the relations between the physiologically characterized neurons and either 1) GABA or 2) dopamine-beta-hydroxylase (DBH), a marker for noradrenergic terminals. GABA-immunoreactive terminals formed numerous direct symmetric synapses on somata and dendrites of pyramidal cells recorded and filled with lucifer yellow (LY). In contrast, in single sections, noradrenergic terminals immunoreactive for DBH rarely contacted LY-filled somata and dendrites. These results support the conclusion that IPSPs observed following single electrical stimulation of the LC region are mediated by GABA, with little involvement of NE. These IPSPs, arising from antidromic invasion of mPFC cells innervating the LC, may improve the signal-to-noise ratio and favor a better responsiveness of neighboring neurons to NE released in the mPFC.

Animals↗

PubMed2002

Medial prefrontal cortex early lesion effects on classical conditioned bradycardia.

The effects of medial prefrontal cortex early lesion (mPFl) on classical conditioned bradycardia (CB) were studied in adult rabbits. In lesioned rabbits, baseline HR, orienting and conditioned HR responses were similar to controls. Since mPFl alone does not affect CB, while it is known to prevent the HR increments produced by a concomitant early cerebellar vermal ablation, medial prefrontal cortex must be involved in the reorganization of the CB control mechanisms following early cerebellar vermal ablation.

Animals↗

PubMed2000

Phonological and semantic fluencies are mediated by different regions of the prefrontal cortex.

Verbal phonological and semantic fluencies were investigated in 24 patients with unilateral prefrontal lesions and 10 normal control subjects. Lesions were limited to small areas within either the dorsolateral (Brodmann's area 46/9) or ventromedial (posterior part of the gyrus rectus) cortices. In a phonological fluency task, patients with lesions to the left dorsolateral region were impaired. In semantic fluency, not only the left dorsolateral group but also the two right frontal damaged groups performed worse than the control group. In agreement with previous studies, our results show that the phonological fluency is mediated by the left dorsolateral prefrontal cortex. In contrast to this, performance on the semantic fluency task depends on a wider portion of the prefrontal cortex involving the left and right dorsolateral and the right ventromedial areas.

Adult↗

PubMed1999

Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS.

Twenty-two depressed adults were scanned with perfusion single-photon computed emission tomography before and after 2 weeks of left perfrontal transcranial magnetic stimulation (TMS) in a parallel design, double-blind treatment study. At medication-free baseline, across all subjects, blood flow in the bilateral medial temporal lobes, left prefrontal cortex, and caudate significantly declined with increased depression severity. Also at baseline, depressed adults who responded to TMS, compared with nonresponders, showed increased inferior frontal lobe activity. Following treatment, there was an even greater difference in inferior frontal blood flow in responders compared with nonresponders, and the negative baseline correlations between depression severity and limbic and prefrontal blood flow disappeared. These results suggest that in depressed adults, 10 days of prefrontal TMS affects prefrontal and paralimbic activity, which may explain its antidepressant effects.

Adult↗

PubMed2003

Long-term potentiation in visual cortical projections to the medial prefrontal cortex of the rat.

In order to investigate neural mechanisms by which the prefrontal cortex adaptively modifies its activities based on past experience, we examined whether or not sensory cortical projections to the medial prefrontal cortex support long-term potentiation (LTP) in rats. Monosynaptic projections from the secondary visual cortex, mediomedial area (V2MM) to the infralimbic cortex were confirmed by orthodromic as well as antidromic activation of single units. High-frequency stimulation (50 Hz, 2 s) induced LTP (approximately 45% increase over the baseline) in the V2MM projection to the infralimbic cortex. LTP induction in this pathway was completely blocked by an injection (i.p.) of CPP, an N-methyl-D-aspartate receptor antagonist. LTP was also induced in the ventral hippocampal projection to the infralimbic cortex by the same high-frequency stimulation. The present results suggest that modification of synaptic weights of afferent sensory cortical projections is one mechanism underlying learning-induced changes in prefrontal cortical neural activities.

Animals↗

PubMed2002

1 hz rTMS over the right prefrontal cortex reduces vigilant attention to unmasked but not to masked fearful faces.

BACKGROUND: Recent repetitive transcranial magnetic stimulation (rTMS) research in healthy subjects suggests that the emotions anger and anxiety are lateralized in the prefrontal cortex. Low-frequency rTMS over the right prefrontal cortex (PFC) shifts the anterior asymmetry in brain activation to the left hemisphere and reduces anxiety. The same rTMS technique results in enhanced anger-related emotional processing, observed as elevations in attention for angry faces. The current study used low-frequency rTMS over the right PFC and indexed selective attention to fearful faces, hypothesizing a reduction in attention for fearful faces, i.e., a reversal of the latter effect. METHODS: In a placebo-controlled design, 1 Hz rTMS at 130% of the individual motor threshold (MT) was applied continuously over the right PFC of eight healthy subjects for 20 minutes. Effects on motivated attention were investigated by means of an emotional Stroop task, indexing selective attention to masked and unmasked fearful faces. RESULTS: Vigilant attention for masked and unmasked fearful faces was observed after placebo stimulation. As hypothesized, rTMS reduced the vigilant emotional response to the fearful face, but only in the unmasked task. CONCLUSIONS: These data provide further support for the lateralization of the emotions anger and anxiety in the prefrontal cortex. In addition, the absence of an effect for masked fearful faces suggests that changes in emotional processing after a single session of rTMS predominantly involve the cortical affective pathways.

Adult↗

PubMed2006

Muscarinic receptor-mediated GTP-Eu binding in the hippocampus and prefrontal cortex is correlated with spatial memory impairment in aged rats.

The present study examined muscarinic receptor/G-protein coupling in the hippocampus and the prefrontal cortex of young and aged Long-Evans rats characterized for spatial learning ability in the Morris water maze. In a highly sensitive time-resolved fluorometry GTP-Eu binding assay, muscarinic-mediated GTP-Eu binding was severely blunted in hippocampus (-32%) and prefrontal cortex (-34%) as a consequence of aging. Furthermore, the magnitude of decreased muscarinic-mediated GTP-Eu binding was significantly correlated with the severity of spatial learning impairment in hippocampus and prefrontal cortex of aged rats and was specifically decreased in the subset of aged rats that were spatial learning impaired when compared to the aged unimpaired and the young rats. Western blot data indicated a preservation of the membrane-bound M1 receptor and the Galphaq/11 protein in both brain regions. These data demonstrate that muscarinic signaling is severely impaired as a consequence of normal aging in a manner that is closely associated with age-related cognitive decline.

Age Factors↗

PubMed1983

Reexamination of functional subdivisions of the rodent prefrontal cortex.

Selective patterns of behavioral deficits were observed on tests of spatial or olfactory learning after different cortical lesions in rats. The results clearly distinguished functional subdivisions of the rodent prefrontal cortex: Rats with lesions of the prefrontal cortex that primarily involve the dorsal bank of the rhinal sulcus were impaired selectively and exhibited increased perseveration of responses in a go, no-go odor discrimination task. In contrast, rats with lesions of the region of prefrontal cortex situated along the medial cortical wall were impaired selectively and exhibited increased perseveration of responses in a spatial delayed alteration task. These behavioral deficits were similar in magnitude and quality to those found in monkeys after discrete ablations of frontal lobe regions that are argued to be homologous prefrontal subdivisions.

Animals↗

PubMed2001

Chronic treatment with reboxetine by osmotic pumps facilitates its effect on extracellular noradrenaline and may desensitize alpha(2)-adrenoceptors in the prefrontal cortex.

1. This study investigated the effect of acute (2 days) and chronic (14 days) treatment with a selective inhibitor of noradrenaline uptake, reboxetine (10 mg kg(-1) day(-1)) by osmotic pumps, on extracellular noradrenaline and the sensitivity of alpha(2)-adrenoceptors in the prefrontal cortex of rats. 2. The effect of continuous infusion of reboxetine for 14 days on cortical extracellular noradrenaline was significantly higher (599% of vehicle levels) than after 2 days (263% of vehicle levels). 3. Brain concentrations of reboxetine after 2 and 14 days of infusion were 37.9+/-17.8 and 37.1+/-7.7 ng g(-1), respectively. 4. Reboxetine infused for 2 and 14 days significantly increased extracellular dopamine in the prefrontal cortex, to a similar extent (257 and 342% of vehicle levels, respectively), whereas extracellular 5-HT was not modified by either treatment. 5. Clonidine (10 and 30 microg kg(-1) i.p.) reduced cortical extracellular noradrenaline similarly in animals treated with reboxetine or vehicle for 2 days whereas the effects in rats infused with reboxetine for 14 days were markedly less than in vehicle-treated animals. 6. Clonidine (0.05 and 0.2 microM), infused through the dialysis probe into the prefrontal cortex, reduced cortical extracellular noradrenaline much less in rats treated with reboxetine for 14 days than in vehicle-treated animals. 7. Reboxetine's effect on extracellular noradrenaline in the prefrontal cortex was greater after chronic treatment and could be associated with desensitization of terminal alpha(2)-adrenoceptors that normally serve to inhibit noradrenaline release.

Adrenergic Uptake Inhibitors↗